1509P - Efficacy and safety of vimseltinib in tenosynovial giant cell tumour (TGCT): Phase II expansion

Background

TGCT is a rare, locally aggressive neoplasm caused by upregulation of the colony-stimulating factor 1 (CSF1) gene, resulting in aberrant CSF1 expression and recruitment of CSF1 receptor (CSF1R)-dependent inflammatory macrophages. Vimseltinib is an oral switch control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. We report safety, efficacy, and preliminary patient-reported outcome data for patients (pts) with TGCT treated with the recommended phase 2 dose (RP2D; 30 mg twice weekly).

Methods

Pts with TGCT not amenable to surgery were treated in 2 cohorts: A (no prior anti-CSF1/CSF1R therapy except imatinib and/or nilotinib) and B (prior anti-CSF1/CSF1R therapy). Objectives were to evaluate efficacy and safety of RP2D. Pain was evaluated using brief pain inventory (BPI) worst and average numeric rating scale scores.

Results

As of Feb 18, 2022, 57 pts with TGCT were enrolled: 46 in A (enrollment complete) and 11 in B (enrollment ongoing). Median age was 45 years (range: 21–71) and the most common location was knee (56%). Objective response rates were 49% and 44% in Cohorts A and B, respectively (Table). Most non-laboratory treatment-emergent adverse events (TEAEs) were grade (G) 1/2; the only G3/4 TEAE observed in >5% of pts was elevated creatine phosphokinase, which was asymptomatic and consistent with the known class effect of CSF1R inhibitors. One pt in Cohort B experienced treatment-related serious AEs of G3 eczema and G2 oedema peripheral. The safety profile was comparable between cohorts and with phase 1 data. Overall, BPI score improvement was observed in >50% of pts at Week 25 (Table). Table: 1509P

^aNo prior anti-CSF1/CSF1R therapy. ^bPrior anti-CSF1/CSF1R therapy. ^cUsing RECIST v1.1 by independent radiologic review; includes all available follow up. Data are maturing and will be updated. ^dImprovement: ≥30% reduction in tumour associated pain at Week 25.

Conclusions

At RP2D, vimseltinib demonstrated encouraging antitumour activity with clinical benefit (partial response + stable disease) in 100% of pts. AEs were manageable in both cohorts. Pts reported symptomatic benefit (improved BPI scores). Results support continued evaluation of vimseltinib in the ongoing phase 3 MOTION trial (NCT05059262).

Clinical trial identification

NCT03069469.

Editorial acknowledgement

Medical writing and editorial support was provided by Lauren Hanlon, PhD, of AlphaBioCom, LLC (King of Prussia, PA, USA) and was funded by Deciphera Pharmaceuticals, LLC (Waltham, MA, USA).

Legal entity responsible for the study

Deciphera Pharmaceuticals, LLC.

Funding

Deciphera Pharmaceuticals, LLC.

Disclosure

J. Blay: Financial Interests, Personal, Advisory Board: Bayer, Deciphera, GSK, Roche; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Invited Speaker: MSD, MSD; Financial Interests, Personal, Other, member of the supervisory board: Innate pharma; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: Astra Zeneca, Roche, Bayer, GSK, Novartis, OSE pharma. H. Gelderblom: Financial Interests, Institutional, Invited Speaker: Daiichi, Deciphera, Novartis, Boehringer Ingelheim, AmMax Bio, Debiopharm, Cytovation. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, , Invited Speaker: Polish Society of Surgical Oncology; Non-Financial Interests, Officer: ASCO; Non-Financial Interests, , Invited Speaker, President Elect: Polish Oncological Society. A. Wagner: Financial Interests, Personal, Advisory Board: Aadi Bioscience, Boerhinger-Ingelheim, Cogent Biosciences, Daiichi-Sankyo, Deciphera, Eli Lilly, Epizyme, Mundipharma; Financial Interests, Institutional, Invited Speaker: Aadi Bioscience, Cogent Biosciences, Daiichi-Sankyo, Deciphera, Eli Lilly, Foghorn Therapeutics, Karyopharm, Plexxikon, Rain Therapeutics; Non-Financial Interests, , Invited Speaker: Sarcoma Alliance for Research Through Collaboation (SARC). M. van de Sande: Financial Interests, Institutional, Research Grant, research grant to department for PhD student: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, registry compensation: Carbofix; Financial Interests, Institutional, Research Grant, clincial research for company product: Implantcast; Financial Interests, Institutional, Invited Speaker, payment to department: Synox Therapeutics Ltd. A. Falcon Gonzalez: Financial Interests, Personal, Advisory Board: Seagen, Novartis, Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Lilly, Grunenthal pharma, Roche. S. Stacchiotti: Financial Interests, Personal, Advisory Board: Bayer, Daiichi, Maxivax, Novartis, Ikena, Astex Pharmaceuticals, Rain Therapeutics; Financial Interests, Personal, Expert Testimony: Bavarian Nordic; Financial Interests, Personal, Invited Speaker: Glaxo Smith Kline, PharmaMar, Aadi; Financial Interests, Institutional, Invited Speaker: Advenchen, Bayer, Deciphera, Epizyme, Glaxo Smith, Karyopharm, PharmaMar, SpringWorks, Hutchison MediPharma International Inc; Financial Interests, Institutional, Funding: Blueprint, Eli Lilly, Daiichi, Novartis, Pfizer; Non-Financial Interests, Invited Speaker, Treasurer: Connective Tissue Oncology; Non-Financial Interests, Advisory Role: Chordoma Foundation, Epithelioid HaemangiondotheliomaFoundation, DesmoidFoundation, Epithelioid Hemangioendothelioma (EHE) Rare Cancer Charity (UK); Non-Financial Interests, , Project Lead, Chair of the systemic therapy committee: EORTC soft tissue and bone sarcoma group; Non-Financial Interests, Leadership Role, President: Italian Sarcoma Group. A. Le Cesne: Financial Interests, Personal, Other, Honoraria: Bayer, PharmaMar, Deciphera. T. Alcindor: Financial Interests, Personal, Advisory Board: Merck, Taiho, Eisai, Pfizer, Roche, BMS, Astra Zeneca, Bayer; Financial Interests, Institutional, Funding, For investigator-initiated trial: EMD Serono; Financial Interests, Personal and Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: Deciphera, Epizyme, Isofol, SpringWorks; Non-Financial Interests, Leadership Role, Co-chair of Esophago-Gastric Disease Site-Oriented Group: Canadian Cancer Trials Group; Non-Financial Interests, Advisory Role, Member, Committee for immunotherapy in upper GI cancers: American Society of Clinical Oncology; Non-Financial Interests, Advisory Role: Colorectal Cancer Canada. C. 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Ravi: Financial Interests, Personal, Stocks/Shares: Tracon Pharma, Merck, AstraZeneca, Pfizer, Moderna Therapeutics; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal and Institutional, Funding: Novartis, Tracon Pharma, Aadi Bioscience, Athenex; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Daiichi Sankyo. A. Casado Herraez: Financial Interests, Personal, Advisory Role: Roche, PharmaMar, EISAI, Merck Sharp & Dohme; Financial Interests, Institutional, Funding: PharmaMar; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: PharmaMar, Roche, Lilly Spain; Financial Interests, Institutional, Other: Lilly. B. Seddon: Financial Interests, Personal, Stocks/Shares, Shares in private healthcare provider company: Leaders in Oncology Care LLP. M. Vallee: Financial Interests, Personal, Full or part-time Employment, I am an employee of Deciphera Pharmaceuticals: Deciphera Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, I own Deciphera Pharmaceuticals stock: Deciphera Pharmaceuticals. R. Jarecha: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, Calyx, Parexel Informatics d/b/a Perceptive Informatics; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals; Non-Financial Interests, Leadership Role, Co-Chair of CT Coordinating Committee, Co-Chair of CT Volumetry Biomarker Committee, Member of Steering Committee, Member of Executive Committee: Radiology Society of North America: Qualitative Imaging Biomarkers Alliance. M. Sharma: Financial Interests, Institutional, Full or part-time Employment, Senior Medical Director, Clinical Development: Deciphera Pharmaceuticals; Financial Interests, Institutional, Stocks/Shares: Deciphera Pharmaceuticals. R. Ruiz-Soto: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, LLC, Immunogen; Financial Interests, Personal, Other, I am an inventor in 3 patents with Immunogen, I transferred the rights to Immunogen. I have not received (and I will not receive) any royalties: Immunogen; Financial Interests, Personal, Other, I am an inventor in pending patents at Deciphera. I have transferred the rights to Deciphera, I have not received (and will not receive) any royalties: Deciphera. M.L. Sherman: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Pieris Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, Pieris Pharmaceuticals. W.D. Tap: Financial Interests, Personal, Advisory Board: Eli Lilly, Daiichi Sankyo, Nano Carrier, Blueprint, Deciphera, C4 Therapeutics, Foghorn Therapeutics, AmMaxBio, MundiBioPharma, Novo Holdings, Servier, Medpacto, Ayala Pharmaceuticals, Kowa Research Institute, Epizyme Inc (Nexus Global Group), Bayer, Cogent Biosciences, Amgen, Aadi Biosciences; Financial Interests, Personal, Invited Speaker: EMD Serono, PER; Financial Interests, Personal, Stocks/Shares: Certis Oncology Solutions, Atropos; Financial Interests, Personal, Other, *patent: - Companion Diagnostics for CDK4 inhibitors (14/854,329); Financial Interests, Institutional, Funding: Novartis, Eli Lilly, Plexxxicon, Daiichi Sankyo, Tracon Pharma, Blueprint Medicines, Immune Design, BioAlta, Deciphera.